TGFb1, esteroides sexuales y matriz extracelular en prolactinomas experimentales.

MARÍA CLARA GUIDA, MVICTORIA RECOUVREUX, DAMASIA BECÚ-VILLALOBOS; GRACIELA DÍAZ-TORGA

Buenos Aires

Congreso; Reunión de la Sociedad Argentina de Biología.; 2008

Sociedad Argentina de Biología

Prolactinomas are the most frequent among pituitary tumors and they are usually benign. TGFâ1 is a cytokine locally synthesized by lactotropes that regulates cellular function, inhibits cell proliferation and prolactin synthesis. TGFâ1 remains inactive by interaction with LAP and other extracellular matrix (EM) components. EM remodeling can cause TGFb1 activation principally by  Thrombospondin-1 (TSP1). The aim of this study was to evaluate TGFb1 expression and regulation in prolactinomas, using as a model adult female rats with  chronic estrogenic or estrogen+progesterone treatment during 4 weeks.  TGFb1 expression, measured by Western blot, was reduced after estrogen (E2) treatment. However, progesterone (P4) co-treatment was able to counteract the estrogen effect. Similarly, TSP1 expression was inhibited by estrogen,  effect which was also prevented by P4 co-treatment.  Pituitary expression of the EM structural component Laminin, was also inhibited by estrogens, but.P4 treatment was unable to counteract the estrogenic effect, and it also inhibited laminin expression per se. Our results suggest a complex TGFb1 regulation by E2 and P4, in which  P4 opposes estrogenic effects normalizing the expression of TGFb1 and its principal activator TSP1. This protective P4 effect could enhance TGFb1 proliferative inhibitor activity, promoting tumor reversal.